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Cytotoxicity of Tumor necrosis factor related apoptosis-inducing ligand towards Ewing's sarcoma cell lines
1Department of Internal Medicine and Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390-8593, USA.
Abstract:
Death ligands of the Tumor Necrosis Factor (TNF) family are known to induce apoptosis upon binding to their cognate receptors. However, the clinical utility of these cytokines as anticancer agents has been limited due to unacceptable toxicity. TRAIL is a recently isolated death ligand that possesses selective anti-tumor activity against a number of cancer cell lines without significant systemic toxicity. In this report we present evidence that cell lines derived from Ewing's Sarcoma (ES) are uniformly sensitive to TRAIL-mediated apoptosis. Furthermore, unlike TNF-alpha, treatment with TRAIL fails to induce the anti-apoptotic and pro-inflammatory NF-kappaB pathway in the ES cell lines. Our results suggest that TRAIL may prove to be a useful agent for the treatment of Ewing's sarcoma and related peripheral neuroectodermal tumors.
Insights
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) shows selective anti-tumor activity. Ewing
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Death ligands, including Tumor Necrosis Factor (TNF) family members, induce apoptosis but often exhibit significant toxicity.
- TRAIL is a death ligand with selective anti-tumor activity and lower systemic toxicity.
- Ewing's Sarcoma (ES) is a challenging pediatric bone cancer.
Purpose of the Study:
- To investigate the efficacy of TRAIL in inducing apoptosis in Ewing's Sarcoma cell lines.
- To determine if TRAIL activates pro-inflammatory pathways like NF-kappaB in ES cells.
Main Methods:
- Treatment of ES cell lines with TRAIL.
- Assessment of TRAIL-mediated apoptosis.
- Analysis of NF-kappaB pathway activation.
Main Results:
- Ewing's Sarcoma cell lines demonstrated uniform sensitivity to TRAIL-induced apoptosis.
- TRAIL treatment did not activate the anti-apoptotic and pro-inflammatory NF-kappaB pathway in ES cells, unlike TNF-alpha.
- TRAIL exhibits selective anti-tumor effects without significant systemic toxicity.
Conclusions:
- TRAIL is a promising therapeutic agent for Ewing's Sarcoma.
- TRAIL's mechanism of action in ES cells bypasses the NF-kappaB pathway, suggesting a favorable toxicity profile.
- Further research into TRAIL for Ewing's Sarcoma and related tumors is warranted.